The bovine mannose 6-phosphate/insulin-like growth factor II receptor. Localization of the insulin-like growth factor II binding site to domains 5-11.

Dahms, Nancy M.; Wick, Debra A.; Brzycki-Wessell, Mary A.

doi:10.1016/s0021-9258(17)41931-4

Cited by 64 publications

(12 citation statements)

References 44 publications

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“…Besides being an endocytic receptor, MPR300 (in contrast to TfR) is a retrograde transported receptor that mainly shuttles between the endosomal compartments and the TGN. 22,74,75 MPR300 delivers acidic hydrolases to lysosomes and is used as a target for treatment of lysosomal storage disorders throughout the body including the CNS. [49][50][51][52]76,77 Zhou et al 77 studied delivery of antibodies against insulin receptor conjugated with MPR300 ligand, idurate-2-sulfate.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells

Siupka

Hersom

Lykke‐Hartmann

et al. 2017

J Cereb Blood Flow Metab

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Brain capillary endothelium mediates the exchange of nutrients between blood and brain parenchyma. This barrier function of the brain capillaries also limits passage of pharmaceuticals from blood to brain, which hinders treatment of several neurological disorders. Receptor-mediated transport has been suggested as a potential pharmaceutical delivery route across the brain endothelium, e.g. reports have shown that the transferrin receptor (TfR) facilitates transcytosis of TfR antibodies, but it is not known whether this recycling receptor itself traffics from apical to basal membrane in the process. Here, we elucidate the endosomal trafficking of the retrograde transported cation-independent mannose-6-phosphate receptor (MPR300) in primary cultures of brain endothelial cells (BECs) of porcine and bovine origin. Receptor expression and localisation of MPR300 in the endo-lysosomal system and trafficking of internalised receptor are analysed. We also demonstrate that MPR300 can undergo bidirectional apical-basal trafficking in primary BECs in co-culture with astrocytes. This is, to our knowledge, the first detailed study of retrograde transported receptor trafficking in BECs, and the study demonstrates that MPR300 can be transported from the luminal to abluminal membrane and reverse. Such trafficking of MPR300 suggests that retrograde transported receptors in general may provide a mechanism for transport of pharmaceuticals into the brain.

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Section: Discussionmentioning

confidence: 99%

Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells

Siupka

Hersom

Lykke‐Hartmann

et al. 2017

J Cereb Blood Flow Metab

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“…The multifunctional CIMPR therefore harbours at least three different ligand binding sites. Since both ␤-glucuronidase and IGF-II at high concentrations partially inhibited binding of uPAR, it is possible that the site for uPAR binding is adjacent to or between repeat 11 and repeat 9, which are important for IGF-II and Man-6-P binding, respectively (Dahms et al, 1993(Dahms et al, , 1994Schmidt et al, 1995). However, the exact location of segments in CIMPR that are important for binding of uPAR must await future experiments.…”

Section: Discussionmentioning

confidence: 99%

“…This may suggest a steric hindrance for binding of uPAR to CIMPR occupied with ␤-glucuronidase. Also, a saturating concentration of IGF-II, which binds to repeat 11 of CIMPR (Dahms et al, 1994;Schmidt et al, 1995) reduced the binding of uPAR. Interestingly, chicken CIMPR does not bind IGF-II (Canfield and Kornfeld, 1989), and uPAR must therefore bind to sites on the receptor different from those that bind IGF-II.…”

Section: Effect Of Ligands To Upar and Cimpr On The Binding Reactionmentioning

confidence: 99%

Mannose 6-Phosphate/Insulin-like Growth Factor–II Receptor Targets the Urokinase Receptor to Lysosomes via a Novel Binding Interaction

Nykjær

Christensen²,

Vorum

et al. 1998

The Journal of Cell Biology

138

117

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The urokinase-type plasminogen activator receptor (uPAR) plays an important role on the cell surface in mediating extracellular degradative processes and formation of active TGF-β, and in nonproteolytic events such as cell adhesion, migration, and transmembrane signaling. We have searched for mechanisms that determine the cellular location of uPAR and may participate in its disposal. When using purified receptor preparations, we find that uPAR binds to the cation-independent, mannose 6-phosphate/insulin-like growth factor–II (IGF-II) receptor (CIMPR) with an affinity in the low micromolar range, but not to the 46-kD, cation-dependent, mannose 6-phosphate receptor (CDMPR). The binding is not perturbed by uPA and appears to involve domains DII + DIII of the uPAR protein moiety, but not the glycosylphosphatidylinositol anchor. The binding occurs at site(s) on the CIMPR different from those engaged in binding of mannose 6-phosphate epitopes or IGF-II. To evaluate the significance of the binding, immunofluorescence and immunoelectron microscopy studies were performed in transfected cells, and the results show that wild-type CIMPR, but not CIMPR lacking an intact sorting signal, modulates the subcellular distribution of uPAR and is capable of directing it to lysosomes. We conclude that a site within CIMPR, distinct from its previously known ligand binding sites, binds uPAR and modulates its subcellular distribution.

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“…The va lue of 10 nl\! un labeled IGF-II lea ding to half-maxim al inhi bition of In a re lated study Dahms et al (24) a na lyzed truncated form s of the bovin e M6PIIGF-II rece ptor transiently expressed in COS cells. Th ey found that a construct encoding repeats 5-11 could be cross-link ed to IGF-II , whereas a construct encoding repea ts 5-10 failed to be cross-li nke d. Th ese res ults showed that the presence of re peat 11 is necessary for the cross-linking to IGF-II .…”

Section: Discussionmentioning

confidence: 99%

“…The exact locations of the binding sites for mannose 6-phosphate and IGF-II still need to be defined. Studies using truncated forms of the extracytoplasmic domain of the bovine M6PIIGF-II receptor indicate that for binding of mannose 6-phosphate repeats 1-3 and 7-9 (22,23), and for binding of IGF-II repeats 5-11 (24) are sufficient.…”

mentioning

confidence: 99%

Localization of the Insulin-like Growth Factor II Binding Site to Amino Acids 1508–1566 in Repeat 11 of the Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor

Schmidt

Kiecke-Siemsen

Waheed

et al. 1995

Journal of Biological Chemistry

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The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) binds insulin-like growth factor II (IGF-II) with high affinity. To localize the IGF-II binding site within the 15 repeating units that form the extracytoplasmic domain of the receptor, purified human M6P/IGF-II receptor was digested with thermolysin, and the fragments were analyzed for their ability to bind 125I-IGF-II in a cross-linking assay. Two IGF-II-binding receptor fragments of 23 and 37 kDa were purified. Sequence analysis revealed that the fragments consist of disulfide connected peptides comprising amino acids 1331-1566 and 1331-1697 of the receptor repeats 9-12. In a second approach we expressed truncated forms of the M6P/IGF-II receptor fused to the C terminus of the extracytoplasmic domain of the 46-kDa mannose 6-phosphate receptor. Fusion proteins containing M6P/IGF-II receptor repeats 10-15, 10-11, or 11-15 bound IGF-II, whereas a fusion protein containing the single repeat 10 failed to bind. This result indicates that repeat 11 (amino acids 1508-1650) is sufficient for binding of IGF-II. Residues 1508-1566, which are shared by the 23-kDa IGF-II-binding fragment and repeat 11, are proposed to form the IGF-II binding site of the M6P/IGF-II receptor.

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The bovine mannose 6-phosphate/insulin-like growth factor II receptor. Localization of the insulin-like growth factor II binding site to domains 5-11.

Cited by 64 publications

References 44 publications

Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells

Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells

Mannose 6-Phosphate/Insulin-like Growth Factor–II Receptor Targets the Urokinase Receptor to Lysosomes via a Novel Binding Interaction

Localization of the Insulin-like Growth Factor II Binding Site to Amino Acids 1508–1566 in Repeat 11 of the Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor

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